The research proposed is focused on physiological interactions between mammals and microorganisms indigenous to their gastro-intestinal tracts. Germfree, gnotobiotic and specific pathogen-free mice and rats are used; certain microbes that associate intimately with mucosal epithelia receive special emphasis. Our long-term goals are to learn how these microbes remain and proliferate in their habitats and how they influence certain physiological responses in their mammalian hosts. In seeking the first goal, we examine the mechanisms by which the microbes adhere to and grow on the epithelia. Microbial culture tecniques are used including methods for culturing oxygen-intolerant anaerobic bacteria. Surface components of the microbial cells are isolated, purified and assayed in systems designed to detect their function in adhesion. In seeking the second goal, we examine the mechanisms by which the indigenous microbiota alters the migration (transit) rate of intestinal epithelial cells. Germfree mice are associated with indigenous microorganisms, with certain physiological properties, e.g., the capacity to 7-alpha-dehydroxylate and/or deconjugate bile acids. The transit time of intestinal enterocytes in these gnotobiotes is compared with that of germfree controls.